Conditional-selex

Abstract

The invention provides method for producing nucleic acid ligands that generate a signal, or cause a decrease in the level of a signal, in the presence of a target molecule or an environmental stimulus. The methods of the instant invention are collectively termed Conditional SELEX. The nucleic acid ligands of the instant invention are useful in any application where it is desirable to measure the concentration of a target molecule or detect and quantitate an environmental stimulus.

What is claimed is:  
     
       1. A nucleic acid ligand to a target molecule, the nucleic acid ligand comprising a prosthetic group, wherein the solvent accessibility of said prosthetic group changes upon the binding of said nucleic acid ligand to said target molecule, and wherein said change in solvent accessibility results in a measurable difference in the properties of said prosthetic group. 
     
     
       2. A nucleic acid ligand responsive to an environmental stimulus selected from the group consisting of pH, ionic strength, light intensity, light wavelength, electromagnetic field, solvent dialectric constant, redox potential, viscosity, and temperature, the nucleic acid ligand comprising a prosthetic group, wherein the solvent accessibility of said prosthetic group changes in the response of the nucleic acid ligand to said environmental stimulus, and wherein said change in solvent accessibility results in a measurable difference in the properties of said prosthetic group. 
     
     
       3. A nucleic acid ligand to a target molecule, the nucleic acid ligand conjugated to a prosthetic group, wherein interaction of said prosthetic group with a cognate ligand changes upon binding of said nucleic acid ligand to said target. 
     
     
       4. A nucleic acid ligand responsive to an environmental stimulus selected from the group consisting of pH, ionic strength, light intensity, light wavelength, electromagnetic field, solvent dialectric constant, redox potential, viscosity, and temperature, the nucleic acid ligand conjugated to a prosthetic group, wherein interaction of said prosthetic group with a cognate ligand changes when said nucleic acid ligand is exposed to said environmental stimulus. 
     
     
       5. A nucleic acid ligand to a target molecule, the nucleic acid ligand comprising a fluorophore, wherein the fluorescence emission spectrum or quantum yield of said fluorophore changes upon binding of said nucleic acid ligand to said target molecule. 
     
     
       6. A nucleic acid ligand responsive to an environmental stimulus selected from the group consisting of pH, ionic strength, light intensity, light wavelength, electromagnetic field, solvent dialectric constant, redox potential, viscosity, and temperature, the nucleic acid ligand comprising a fluorophore, wherein the fluorescence emission spectrum or quantum yield of said fluorophore changes when said nucleic acid ligand is exposed to said environmental stimulus. 
     
     
       7. A nucleic acid ligand to a target molecule, wherein the nucleic acid ligand is conjugated to a non-fluorescent fluorogenic group, and wherein said fluorogenic group undergoes intramolecular bond cleavage to generate a fluorescent signal when said nucleic acid ligand binds to said target. 
     
     
       8. A nucleic acid ligand responsive to an environmental stimulus selected from the group consisting of pH, ionic strength, light intensity, light wavelength, electromagnetic field, solvent dialectric constant, redox potential, viscosity, and temperature, wherein the nucleic acid ligand is conjugated to a non-fluorescent fluorogenic group, and wherein said fluorogenic group undergoes intramolecular bond cleavage to generate a fluorescent signal when said nucleic acid ligand is exposed to said environmental stimulus. 
     
     
       9. A nucleic acid ligand to a target molecule, wherein said nucleic acid ligand is conjugated to a prosthetic group, said prosthetic group modified such that it does not interact with a cognate ligand of said prosthetic group, wherein said modified prosthetic group undergoes intramolecular bond rearrangement allowing interaction with said cognate ligand when said nucleic acid ligand binds to said target. 
     
     
       10. A nucleic acid ligand responsive to an environmental stimulus selected from the group consisting of pH, ionic strength, light intensity, light wavelength, electromagnetic field, solvent dialectric constant, redox potential, viscosity, and temperature, wherein said nucleic acid ligand is conjugated to a prosthetic group, said prosthetic group modified such that it does not interact with a cognate ligand of said prosthetic group, wherein said modified prosthetic group undergoes intramolecular bond rearrangement allowing interaction with said cognate ligand when said nucleic acid ligand is exposed to said environmental stimulus. 
     
     
       11. A nucleic acid ligand to a target molecule, wherein said nucleic acid ligand binds to a detectable molecule only when said nucleic acid ligand is bound to said target. 
     
     
       12. A nucleic acid ligand responsive to an environmental stimulus selected from the group consisting of pH, ionic strength, light intensity, light wavelength, electromagnetic field, solvent dialectric constant, redox potential, viscosity, and temperature, wherein said nucleic acid ligand binds to a detectable molecule only when said nucleic acid ligand is exposed to said environmental stimulus.